RT Journal Article
SR Electronic
T1 NMDA receptors on dopaminoceptive neurons are essential for drug-induced conditioned place preference
JF eneuro
JO eneuro
FD Society for Neuroscience
SP ENEURO.0084-15.2016
DO 10.1523/ENEURO.0084-15.2016
A1 Magdalena Sikora
A1 Krzysztof Tokarski
A1 Bartosz Bobula
A1 Joanna Zajdel
A1 Kamila Jastrzębska
A1 Przemysław Eligiusz Cieślak
A1 Magdalena Zygmunt
A1 Joanna Sowa
A1 Magdalena Smutek
A1 Katarzyna Kamińska
A1 Krystyna Gołembiowska
A1 David Engblom
A1 Grzegorz Hess
A1 Ryszard Przewlocki
A1 Jan Rodriguez Parkitna
YR 2016
UL http://www.eneuro.org/content/early/2016/05/25/ENEURO.0084-15.2016.abstract
AB Plasticity of the brain’s dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1D1CreERT2 mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for Pavlovian or instrumental conditioning. However, NR1D1CreERT2 mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine or ethanol, although these mice acquired a preference for sacharose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.Significance Statement: We find that removing the NMDA receptor, which is a regulator of plasticity in excitatory synapses, in a subpopulation of neurons receiving dopamine signals disrupted the rewarding effects of drugs of abuse within their environmental context. Simultaneously, the NMDA receptor loss had no effect on the memory of a context associated with a natural reward or with an aversive substance. This observation supports the hypothesis that neuronal mechanisms processing natural and drug rewards differ and shows that NMDA receptors in a subgroup of dopaminoceptive neurons are essential specifically in the latter case.